Carotid Artery Stenting Versus

Transcription

1 Carotid Artery Stenting Versus Carotid Endarterectomy Seong-Wook Park, MD, PhD, FACC,, Seoul, Korea

2 Stroke & Carotid artery stenosis

3 Stroke & Carotid artery stenosis Cerebrovascular disease is one of the leading cause of the death, with an annual stroke rate of approximately 2.4% of the population p Carotid artery stenosis is responsible for about 25% of stroke Population-based studies : carotid stenosis-0.5% 05% in the sixth decade and increased to 10% in persons over 80 years of age. The majority of patients are asymptomatic (70-80%)

4 Natural Incidence of CVA In Carotid Stenosis Asymptomatic >80% carotid stenosis - 1.9%/ year (ECST registry) - 12% / 5 year (ACAS, ACST) Symptomatic >70% carotid stenosis - 11% / year - 40% / 5 years

5 CEA vs. Medical Rx Symptomatic Patients (DS 70%) Deat th or Str roke (% %) CEA Medical therapy 30 P<0.01 P=0.011 P< ECST VA NASCET

6 CEA vs. Medical Rx Asymptomatic Patients (DS > 60%) Deat th or Str roke (% %) CEA Medical therapy 25 P=NS P<0.01 P<0.001 P< CASANOVA VA ACAS ACST

7 Carotid EndArterectmy; CEA

8 Indications for carotid artery revascularization i Indication level Symptomatic stenosis Asymptomatic stenosis Proven Acceptable Unacceptable 70-99% stenosis Periprocedural complication risk <6% > 80% stenosis Periprocedural complication risk <3% Life expectancy > 5yrs > 60% stenosis Periprocedural complication risk <3% Planned CABG < 60% stenosis or Periprocedural complication risk >3% No indication for CABG 70% 80% 50-69% stenosis Periprocedural complication risk <6% 50% 60% <29% stenosis, or Periprocedural complication risk > 6% Circulation 2006;113:

9 Carotid Artery Stenting Current status Embolic protection device (EPD) is mandatory in CAS

10 Embolic Protection Devices (EPD) ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical i l Expert Consensus Document on Carotid Stenting J Am Coll Cardiol 2007;49:126 70

11 Carotid Stent Trial Data Pre-EPD Normal risk/randomized - WallStent trial-1999 (223) Post-EPD Normal risk/symptomatic and asymptomatic/randomized - CREST, ACT 1 Normal risk/symptomatic/randomized - EVA-3S, SPACE, CAVATAS 2 Normal risk/non-randomized - CARESS-2003 (143) High risk/randomized - SAPPHIRE-2002 (334) High risk/registry - SAPPHIRE-2002 (406) - ARCHeR-2003 (581) - SECuRITY-2003 (305) - BEACH-2004 (408) - CABERNET-2004 (454) - CREATE (413)

12 Symptomatic high surgical risk & Asymptomatic high surgical risk

13 CAVATAS CEA vs. Angioplasty without protection in Low and High Surgical Risk group Angioplasty CEA N=251 N= day death & stroke Cranial neuropathy 1-year restenosis (>70% DS)* 3-year death or disabling stroke 64% 6.4% 0 % 14 % 14.3 % 59% % 4 % 14.2 % * Stenting = only in 26% Lancet 2001;357:

14 SAPPHIRE CEA vs. CAS with Filter From August 2000 to July 2002 Carotid a stenosis with high risk (n=334) High-risk iksx 50% &AS ASx 80% Randomization (1:1) Carotid Stenting with filter device (n=167) Carotid endarterectomy (n=167) Primary endpint: composite of death, stroke, or myocardial Infarction within 30 days or death or ipsilateral stroke btw 31days and 1 year Yadav JS, et al. NEJM 2004;351:1493

15 CEA vs. CAS with Filter SAPPHIRE 30-Day Outcomes Death /MI /Stroke Cranial nerve palsy % P= P< CAS + Filter CEA 0 0 CAS + Filter CEA Yadav JS, et al. NEJM 2004;351:1493

16 CEA vs. CAS with Filter SAPPHIRE 30-Day Outcomes Symptomatic ti patients t Asymptomatic ti patients t % Death /MI /Stroke P= CAS + Filter 9.3 CEA % Death /MI /Stroke P= CAS + Filter CEA Yadav JS, et al. NEJM 2004;351:1493

17 CEA vs. CAS with Filter SAPPHIRE MAE Fre ee Surv vival (% %) Year Clinical Outcomes P=0.053 CAS (n=167) CEA (n=167) Primary endpoint: composite of death, stroke, or MI within 30 days or death or ipsilateral stroke between 31 days and 1 year Days After Procedure Yadav JS, et al. NEJM 2004;351:1493

18 CEA vs. CAS with Filter SAPPHIRE 1-Year Clinical Outcomes Primary endpoint: composite of death, stroke, or MI within 30 days or death or ipsilateral il l stroke between 31 days and 1 year Symptomatic patients Asymptomatic patients % 20 P= CAS + Filter 16.5 CEA % 25 P= CAS + Filter 21.5 CEA Yadav JS, et al. NEJM 2004;351:1493

19 CEA vs. CAS with Filter SAPPHIRE 1-Year repeat revascularization % 5 4 P= CAS + Filter CEA Yadav JS, et al. NEJM 2004;351:1493

20 SAPPHIRE Conclusion Among patients with severe carotidartery stenosis in high risk group, carotid artery stenting (CAS) with the use of an emboli-protection device is not inferior to carotid endarterectomy (CEA). Yadav JS, et al. NEJM 2004;351:1493

21 CEA vs. CAS with or without EPD % 30 days outcomes from 5 RCT (n=1269) (CAVATAS, Kentucky A&B, Leicester, WALL STENT, SAPPHIRE) Death / any stroke Death / disabling stroke % OR, 1.33; CI, OR, 1.22; CI, CAS CEA CAS CEA Coward LJ, et al. Stroke 2005;36:

22 CEA vs. CAS with or without EPD Outcomes from 5 RCT (n=1269) (CAVATAS, Kentucky A&B, Leicester, WALL STENT, SAPPHIRE) % 20 Death /any 1 year % Cranial nerve palsy 10 OR, 1.01; CI, OR, 0.13; CI, CAS CEA CAS CEA Coward LJ, et al. Stroke 2005;36:

23 ARCHeR CES vs. CAS with Accunet Multicenter, prospective, nonrandomized Carotid stenosis (n=581) High-risk Sx & Asx patients Carotid Stenting with Accunet (n=581) Carotid endarterectomy (Historical control) Primary endpint: composite of periprocedural death, stroke, or myocardial Infarction within 30 days, plus ipsilateral stroke btw 31days and 1 year Gray WA, et al. J Vasc Surg 2006;44:258-69

24 CEA vs. CAS with Accunet ARCHeR 30-Day and 1-year Outcomes % 30-day outcomes % year outcomes Death/stroke/MI CAS + Filter Death/stroke 0 CAS+filter CEA Gray WA, et al. J Vasc Surg 2006;44:258-69

25 Symptomatic normal risk & Asymptomatic normal risk

26 CaRESS CES vs. CAS with GuardWire Multicenter, prospective, nonrandomized 1:2 ratio Carotid a stenosis (n=397) Normal-risk Sx & Asx patients Carotid Stenting with GuardWire (n=143) Carotid endarterectomy (n=254) Primary endpint: death and stroke at 30 days and a composite of death, stroke, or myocardial Infarction within 30 days and death or stroke btw 31days and 1 year J Vasc Surg 2005;42:213-9

27 CEA vs. CAS with GuardWire CaRESS 30-Day and 1-year Outcomes Death / stroke at 30 days Death / stroke at 1 year % P=NS % P=NS CAS CEA CAS CEA J Vasc Surg 2005;42:213-9

28 Carotid Stenting Clinical trials for normal risk Carotid Artery Disease Patients 25% 75% Symptomatic Asymptomatic 15% 10% 50% 25% Normal Risk High Risk Normal Risk High Risk SPACE EVA-3S 1727 patients Recent NEGATIVE RCT s???

29 EVA-3S Ed Endarterectomy t versus stenting ti in patients t with symptomatic severe carotid stenosis 872 initially planned Symptomatic carotid stenosis of 60% or more N=527: randomization EVA-3S CEA (n=259) CAS (n=261) Primary end point: incidence of any stroke or death within 30 days after treatment e t Non inferiority design Hypothesis (stroke+death): 4% CAS vs. 5.6% CEA NEJM 2006;355:

30 EVA-3S EVA Major eligibility Criteria Inclusion criteria Age 18yrs Hemispheric or retinal transient ischemic attack or nondisabling stroke (or retinal infarct) within 120 days before enrollment Stenosis 60% in symptomatic carotid artery Exclusion criteria Modified Rankin S 3 Severe tandem lesion Previous Hx. (CEA,CAS) Uncontrolled HT or DM Unstable angina Contra-Ix. of heparin, clopidogrel Hx. of bleeding disorder Life expectancy < 2yr

31 EVA-3S Day Outcomes % 9.6% 8 P= % CEA CAS Relative risk: 2.5 (95% CI, 1.2 to 5.1) NEJM 2006;355:

32 EVA-3S 6 Months Events % 6.1% CEA P= % CAS Events: any stroke or death after treatment NEJM 2006;355:

33 EVA-3S Conclusion In patients with symptomatic carotid stenosis of 60% or more, the rates of death and stroke at 1 and 6 months were lower with endarterectomy than with stenting NEJM 2006;355:

34 Limitation EVA-3S Early in the EVA-3S trial, protection from embolism was not used among patients who underwent stenting, and the incidence of stroke was 25% (5 of 20). -Protection device was used in 91.9% of carotid stenting arm. Learning curve for carotid stenting; Involved center had a variable degree of experience in CAS. -Five different stents, seven different protection devices, and experience with two procedures was required for any new device used. NEJM 2006;355:

35 Limitation EVA-3S Although h the angiographic appearance of fthe lesion was not an eligibility criterion, plaque morphology (length, degree of ulceration, and presence or absence of thrombus) could be related to complication rates for stenting. 42 and 36 patients who underwent stenting in the EVA-3S trial received only single (unspecified) antiplatelet therapy before and after the procedure, respectively. NEJM 2006;355:

36 30 days results from SPACE trial in symptomatic patients Randomized non-inferiority trial: 1900 initially planned 1200 patients with severe carotid stenosis (>70%) and recent neurological symptoms (< 180 days) 567 treated with CAS 18 not treated 14 treated with CEA 565 treated with CEA 12 not treated 6 treated with CAS 1 died before Tx. 599: Protected 27% randomised patients included on an intention-to-treat basis for analysis Lancet 2006;368;

37 Primary endpoint Ipsilateral stroke (ischemic stroke or intracerebral bleeding or both, with symptoms lasting more than 24 hr) or death of any cause between randomization and 30 days after Treatment. Null hypothesis The difference between the events rates in CAS and CEA group was 2.5% or more. Non-inferiority margin defined as less than 2.5% on the basis of an expected event rate 5% SPACE Lancet 2006;368;

38 Outcome events up to 30 days SPACE Number (%) Absolute diff. Odds ratio CAS (n=599) Primary endpoint 41 (6.84%) Ipsilateral ischemic stroke 39 (6.51%) Ipsilateral intracerebral 1 bleeding (0.18%) Death 4 (0.67%) CEA (n=584) 37 (6.34%) 30 (5.14%) 5 (0.86%) 5 (0.86%) CAS-CEA (90% CI) 0.51* (-2.37 to 3.39) *One-sided p value for non-inferiority is 0.09 CAS/CEA (95% CI) 1.09 (0.69 to 1.72) 1.26 (0.77 to 2.18) 0.19 (0.004 to 1.74) 0.78 (0.15 to 3.64)

39 SPACE 6 Months Results CAS CEA P=0.66 P=0.46 P= Primary endpoint Ipsilateral infarction Ipsilateral infarction or death TCT 2007

40 SPACE 1 Year Results CAS CEA 1.14 ( ) 1.98 ( ) 0.90 ( ) Ipsilateral stroke or vascular death Recurrent restenosis (>70% ECST by US) Every stroke TCT 2007

41 Limitation of SPACE trial SPACE Actual difference (90% CI) for primary endpoint in SPACE. Because upper CI is more than 2.5, study has failed to show non-inferiority for carotid angioplasty and stenting (CAS). However, because CIs cross zero, difference in primary outcome between carotid endarterectomy and carotid angioplasty and stenting was not statistically significant. Lancet 2006;368;

42 SPACE Limitation of SPACE trial Only 27% (n=151) of patients used embolic protection ti devices Study underpowered: with the current event rates, a sample size of >2,500 would be needed - Running out of funds - Slow enrollment: pts in 4 years Lancet 2006;368;

43 Limitation of SPACE trial SPACE Despite SPACE being the biggest trial to date, one is left with the unavoidable conclusion that it was stopped prematurely. Notwithstanding funding issues, the planned margin of non-inferiority (<2.5%) was based on a power calculation of 1900 patients and this larger sample might hthave provided dmuch htighter CIs and more robust statistical data. Lancet 2006;368;

44 SPACE Conclusion Although SPACE failed to prove non-inferiority of CAS compared with CEA for the periprocedural complication rate, which was statistically not significant (p=0.09) 09) No statistical difference of primary and secondary end points up to 1 year Lancet 2006;368;

45 Meta-analysis of randomized trials Protected CAS vs. CEA Death & stroke at 30 day Relative risk meta-analysis (random effect) SAPPHIRE 0.89 ( ) SPACE EVA-3S 108( ( ) 2.48 ( ) Combined (random) 1.34 ( ) TCT 2007

46 Randomized CAS vs. CEA ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on Carotid Stenting J Am Coll Cardiol 2007;49:126 70

47 Carotid Stenting Clinical trials for normal risk Carotid Artery Disease Patients 25% 75% Symptomatic Asymptomatic 15% 10% 50% 25% Normal Risk High Risk Normal Risk High Risk CREST CREST CREST = 1400/2500 ACT 1 ACT 1 = 300/1580 On going trials ascertain this issues

48 Vascular Medicine Perspective: CEA versus Stentt High risk symptomatic patient (>50%) carotid stenting is preferred and reimbursed High risk asymptomatic patient (>80%) carotid stenting is preferred and reimbursed Normal risk symptomatic patient (>50%) :CaRESS, SPACE, EVA-3S More data are needed (CAVATAS-2, CREST) Normal risk asymptomatic patient (>80%) :CaRESS, More data are needed (CREST, ACT1)

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